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Last update 08 May 2025

PARS2

Last update 08 May 2025

Basic Info

Synonyms

DKFZp727A071, PARS2, Probable proline--tRNA ligase, mitochondrial

+ [3]

Introduction

Mitochondrial aminoacyl-tRNA synthetase that catalyzes the specific attachment of the proline amino acid (aa) to the homologous transfer RNA (tRNA), further participating in protein synthesis. The reaction occurs in a two steps: proline is first activated by ATP to form Pro-AMP and then transferred to the acceptor end of tRNA(Pro).

Drugs associated with PARS2

Halofuginone derivative 3

Target

PARS2

Mechanism

PARS2 inhibitors

Active Org.

Sun Yat-Sen University

Originator Org.

Sun Yat-Sen University

Active Indication

Bacterial Infections

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PARS2

100 Translational Medicine associated with PARS2

0 Patents (Medical) associated with PARS2

Literatures (Medical) associated with PARS2

01 Jul 2025·European Journal of Medicinal Chemistry

Development of potent inhibitors targeting bacterial prolyl-tRNA synthetase through fluorine scanning-directed activity tuning

Article

Author: Qiu, Haipeng ; Gu, Qiong ; Luo, Zhiteng ; Liu, Hongwei ; Chen, Bingyi ; Peng, Xiaoying ; Zhou, Huihao ; Tan, Qingyun

As essential enzymes encoded by single genes, aminoacyl-tRNA synthetases (aaRSs) have long been considered promising drug targets for combating microbial infections. In this study, we developed a novel class of amino acid-ATP dual-site inhibitors of prolyl-tRNA synthetase (ProRS) through the structural simplification of the intermediate product prolyl adenylate and its non-hydrolyzable mimic. The co-crystal structures of the compound PAA-5 bound to both Pseudomonas aeruginosa and human cytoplasmic ProRSs (PaProRS and HsPrors) were solved to high resolution. Utilizing the structural information gained, a fluorine scanning (F-scanning) strategy was applied to PAA-5, and the biochemical and biophysical assays demonstrated that fluorine substitutions at specific positions of PAA-5 selectively enhanced its activity against bacterial ProRS. The dual-fluorinated derivative PAA-38 exhibited the highest antibacterial potency, with a K_d value of 0.399 ± 0.074 nM and an IC₅₀ value of 4.97 ± 0.98 nM against PaProRS and an MIC value of 4-8 μg mL^-1 against tested bacterial strains. Our study provides a novel lead compound for the development of aaRS-based antibiotics and highlights F-scanning as a powerful strategy for lead optimization, particularly in pinpointing the subtle fluorophilic environments within the protein pocket to achieve better activity and selectivity.

01 Dec 2024·Biocomputing 2025

Plasma protein-based and polygenic risk scores serve complementary roles in predicting inflammatory bowel disease

Article

Author: Greenplate, Allison R. ; Woerner, Jakob ; Shivakumar, Manu ; Kim, Dokyoon ; Lee, Seunggeun ; Apostolidis, Sokratis A. ; Jeong, Seokho ; Nam, Yonghyun ; Westbrook, Thomas

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), has a significant genetic component and is increasingly prevalent due to environmental factors. Current polygenic risk scores (PRS) have limited predictive power and cannot inform time of symptom onset. Circulating proteomics profiling offers a novel, non-invasive approach for understanding the inflammatory state of complex diseases, enabling the creation of proteomic risk scores (ProRS). This study utilizes data from 51,772 individuals in the UK Biobank to evaluate the unique and combined contributions of PRS and ProRS to IBD risk prediction. We developed ProRS models for CD and UC, assessed their predictive performance over time, and examined the benefits of integrating PRS and ProRS for enhanced risk stratification. Our findings are the first to demonstrate that combining genetic and proteomic data improves IBD incidence prediction, with ProRS providing time-sensitive predictions and PRS offering additional long-term predictive value. We also show that the ProRS achieves better predictive performance among individuals with high PRS. This integrated approach highlights the potential for multi-omic data in precision medicine for IBD.

08 Jul 2024·Nucleic Acids Research

Adaptation of a eukaryote-like ProRS to a prokaryote-like tRNAPro

Article

Author: Amrullah, Luqman Fikri ; Wang, Chien-Chia ; Liu, Shih-Yang ; Yang, Chih-Shiang ; Latifah, Emi ; Tseng, Yi-Kuan ; Ivanesthi, Indira Rizqita ; Chuang, Tsung-Hsien ; Pan, Hung-Chuan

AbstractProlyl-tRNA synthetases (ProRSs) are unique among aminoacyl-tRNA synthetases (aaRSs) in having two distinct structural architectures across different organisms: prokaryote-like (P-type) and eukaryote/archaeon-like (E-type). Interestingly, Bacillus thuringiensis harbors both types, with P-type (BtProRS1) and E-type ProRS (BtProRS2) coexisting. Despite their differences, both enzymes are constitutively expressed and functional in vivo. Similar to BtProRS1, BtProRS2 selectively charges the P-type tRNAPro and displays higher halofuginone tolerance than canonical E-type ProRS. However, these two isozymes recognize the primary identity elements of the P-type tRNAPro―G72 and A73 in the acceptor stem―through distinct mechanisms. Moreover, BtProRS2 exhibits significantly higher tolerance to stresses (such as heat, hydrogen peroxide, and dithiothreitol) than BtProRS1 does. This study underscores how an E-type ProRS adapts to a P-type tRNAPro and how it may contribute to the bacterium's survival under stress conditions.

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